, Volume 40, Issue 3, pp 1062–1071 | Cite as

Elevated Galectin-9 Suppresses Th1 Effector Function and Induces Apoptosis of Activated CD4+ T Cells in Osteoarthritis

  • Shufeng Yang
  • Jin Wang
  • Fengrong Chen
  • Guoyin Liu
  • Zhiqiang WengEmail author
  • Jianmin ChenEmail author


T cell immunoglobulin and mucin domain 3 (Tim-3) is a critical regulatory molecule found on activated Th1 cells, exhausted CD8+ T cells, and resting monocytes/macrophages. Galectin-9 (Gal-9) is an identified ligand for Tim-3. Interaction between Tim-3 and Gal-9 is thought to inhibit Th1 responses. The regulation and function of Tim-3 and Gal-9 in osteoarthritis (OA) have not been intensively investigated. We found that in peripheral blood, CD4+ T cells, but not CD8+ T cells or CD14+ monocytes, from OA patients presented significantly elevated Tim-3 and Gal-9 expression compared to those from healthy controls (HC). The CD4+ T cells from OA did not present altered Th1, Th2, and Th17 composition in the peripheral blood, but secreted less Th1 cytokine interleukin 2 (IL-2) and interferon gamma (IFN-γ) after activation. Further investigation demonstrated that Gal-9 induced high levels of apoptosis in activated CD4+ T cells from OA patients. Inhibition of Gal-9 resulted in significantly higher IL-2 and IFN-γ expression that was directly correlated with the number of non-apoptotic cells. In the synovial fluid, both secreted Gal-9 and surface Gal-9 levels were significantly higher in less-severe grade 2 OA patients than in more-severe grade 4 OA patients. Surface Tim-3 was also higher in synovial fluid CD8+ T cells and CD14+ monocytes from grade 2 OA patients and lower in grade 4 OA patients. Together, these results suggested that Tim-3 and Gal-9 could downregulate T cell inflammation in OA, and could be utilized as a novel therapeutic strategy.


galectin-9 osteoarthritis Tim-3 



This work was supported by Nanjing Science and Technology Project (201503007), The Science and Innovation Program of Nanjing Military Command (15ZD020), and Science and Research Fund of Xiamen Municipal Planning Commission (No.: 3502Z20149015).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of OrthopedicsBayi Hospital Affiliated Nanjing University of Chinese MedicineNanjingPeople’s Republic of China
  2. 2.Department of OrthopedicsXiamen University Affiliated Chenggong HospitalXiamenPeople’s Republic of China
  3. 3.Department of Outpatient, Jinling HospitalNanjing University School of MedicineNanjingPeople’s Republic of China

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